Alzheimer’s disease is marked by the buildup of sticky protein clumps in the brain called amyloid plaques. Many new treatments are designed to remove these plaques, but scientists still do not fully understand an important question: are all plaques equally harmful, or are newly formed plaques more damaging to brain cells than older ones? The answer could have major implications for how and when Alzheimer’s drugs are used.
This project brings together an international team of researchers led by Professors Frances Edwards (University College London) and Jörg Hanrieder (University of Gothenburg). Their goal is to determine how the age of amyloid plaques affects brain health and communication between neurons.
To do this, the team uses a powerful labeling approach that allows them to “timestamp” plaques as they form, making it possible to distinguish newly deposited plaques from those that formed much earlier in life. This is especially important because Alzheimer’s disease develops slowly over decades in humans. To better reflect this process, the researchers studied older mice that develop plaques gradually with age, rather than rapidly, as many laboratory models do. These experiments required years of preparation. The mice had to be carefully bred and aged for nearly two years while receiving specialized diets that allow plaque labeling. When the original U.S. National Institutes of Health (NIH) grant supporting this work was unexpectedly terminated due to international funding restrictions, the most critical phase of the study was just beginning. At that point, the animals had already undergone live brain recordings, and their brains were preserved and are now ready for detailed analysis.
With one additional year of support, this project will allow the team to complete this uniquely valuable work. Brain tissue will be analyzed in London to map how neurons are connected, and in Gothenburg to examine plaque types and changes in brain chemistry. Completing these analyses will preserve a rare, time-sensitive dataset and provide insights into whether targeting specific plaque populations could improve Alzheimer’s treatments. By enabling the completion of this study, CureAlz support ensures that years of careful preparation and investment are not lost and helps advance our understanding of how amyloid plaques contribute to Alzheimer’s disease and how best to intervene.
